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Increased positive selection of B1 cells and reduced B cell tolerance to intracellular antigens in C1q-deficient mice

Ferry, H; Potter, PK; Crockford, TL; Nijnik, A; Ehrenstein, MR; Walport, MJ; Botto, M; (2007) Increased positive selection of B1 cells and reduced B cell tolerance to intracellular antigens in C1q-deficient mice. J IMMUNOL , 178 (5) 2916 - 2922.

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Abstract

Inherited deficiency of early components of the classical complement pathway is strongly associated with the targeting of intracellular self Ags in systemic lupus erythematosus, but the reasons for this association are debated. In this study, we show that C1q deficiency increases the positive selection of B1b B cells and IgM autoantibodies by an intracellular self Ag, which is exposed on dying cells, and decreases the negative selection of autoreactive conventional B cells by the same Ag. These effects are specific to intracellular Ag because C1q deficiency does not affect negative selection by extracellular self Ag or increase the positive selection of naive B cells. The B1-derived IgM autoantibody binds to the intracellular Ag when it is expressed on dying cells, leading to fixation of C1q and clearance of cells by phagocytosis. These findings suggest that the positive selection of autoreactive B1 cells by self Ags may contribute to the IgM and C1q-dependent clearance of dying cells in a feedback loop that limits exposure of conventional B cells to immunogenic self Ags. We show that exposure of intracellular Ag leads to the activation of conventional B cells, when there is a source of T cell help in vivo.

Type: Article
Title: Increased positive selection of B1 cells and reduced B cell tolerance to intracellular antigens in C1q-deficient mice
Keywords: SYSTEMIC-LUPUS-ERYTHEMATOSUS, NATURAL IMMUNOGLOBULIN-M, APOPTOTIC CELLS, AUTOANTIBODY PRODUCTION, COMPLEMENT ACTIVATION, MATURATION ANTIGEN, CLASSICAL PATHWAY, SELF-TOLERANCE, C1Q DEFICIENCY, ANTIBODIES
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation
URI: http://discovery.ucl.ac.uk/id/eprint/569308
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